Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery

Ilaria Cataudella; Ala Trusina; Kim Sneppen; Kenn Gerdes; Namiko Mitarai

doi:10.1093/nar/gks297

Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery

Ilaria Cataudella, Ala Trusina, Kim Sneppen, Kenn Gerdes, Namiko Mitarai

59 Citations (Scopus)

Abstract

Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called `conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli. We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated.

Original language	English
Journal	Nucleic Acids Research
Volume	40
Issue number	14
Pages (from-to)	6424-6434
Number of pages	11
ISSN	0305-1048
DOIs	https://doi.org/10.1093/nar/gks297
Publication status	Published - Aug 2012
Externally published	Yes

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10.1093/nar/gks297

Cite this

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title = "Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery",

abstract = "Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called `conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli. We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated.",

author = "Ilaria Cataudella and Ala Trusina and Kim Sneppen and Kenn Gerdes and Namiko Mitarai",

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T1 - Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery

AU - Cataudella, Ilaria

AU - Trusina, Ala

AU - Sneppen, Kim

AU - Gerdes, Kenn

AU - Mitarai, Namiko

PY - 2012/8

Y1 - 2012/8

N2 - Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called `conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli. We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated.

AB - Many toxin-antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called `conditional cooperativity' as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli. We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated.

U2 - 10.1093/nar/gks297

DO - 10.1093/nar/gks297

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